Individualized treatment rules/recommendations (ITRs) aim to improve patient outcomes by tailoring treatments to the characteristics of each individual. However, when there are many treatment groups, existing methods face significant challenges due to data sparsity within treatment groups and highly unbalanced covariate distributions across groups. To address these challenges, we propose a novel calibration-weighted treatment fusion procedure that robustly balances covariates across treatment groups and fuses similar treatments using a penalized working model. The fusion procedure ensures the recovery of latent treatment group structures when either the calibration model or the outcome model is correctly specified. In the fused treatment space, practitioners can seamlessly apply state-of-the-art ITR learning methods with the flexibility to utilize a subset of covariates, thereby achieving robustness while addressing practical concerns such as fairness. We establish theoretical guarantees, including consistency, the oracle property of treatment fusion, and regret bounds when integrated with multi-armed ITR learning methods such as policy trees. Simulation studies show superior group recovery and policy value compared to existing approaches. We illustrate the practical utility of our method using a nationwide electronic health record-derived de-identified database containing data from patients with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma.
The generalized g-formula can be used to estimate the probability of survival under a sustained treatment strategy. When treatment strategies are deterministic, estimators derived from the so-called efficient influence function (EIF) for the g-formula will be doubly robust to model misspecification. In recent years, several practical applications have motivated estimation of the g-formula under non-deterministic treatment strategies where treatment assignment at each time point depends on the observed treatment process. In this case, EIF-based estimators may or may not be doubly robust. In thi…
In precision medicine, Dynamic Treatment Regimes (DTRs) are treatment protocols that adapt over time in response to a patient's observed characteristics. A DTR is a set of decision functions that takes an individual patient's information as arguments and outputs an action to be taken. Building on observed data, the aim is to identify the DTR that optimizes expected patient outcomes. Multiple methods have been proposed for optimal DTR estimation with continuous outcomes. However, optimal DTR estimation with binary outcomes is more complicated and has received comparatively little attention. Sol…
Randomized clinical trials with time-to-event outcomes have traditionally used the log-rank test followed by the Cox proportional hazards (PH) model to estimate the hazard ratio between the treatment groups. These are valid under the assumption that the right-censoring mechanism is non-informative, i.e. independent of the time-to-event of interest within each treatment group. More generally, the censoring time might depend on additional covariates, and inverse probability of censoring weighting (IPCW) can be used to correct for the bias resulting from the informative censoring. IPCW requires a…
The present paper deals with the problem of allocating patients to two competing treatments in the presence of covariates or prognostic factors in order to achieve a good trade-off among ethical concerns, inferential precision and randomness in the treatment allocations. In particular we suggest a multipurpose design methodology that combines efficiency and ethical gain when the linear homoscedastic model with both treatment/covariate interactions and interactions among covariates is adopted. The ensuing compound optimal allocations of the treatments depend on the covariates and their distribu…
In the absence of data from a randomized trial, researchers often aim to use observational data to draw causal inference about the effect of a treatment on a time-to-event outcome. In this context, interest often focuses on the treatment-specific survival curves; that is, the survival curves were the entire population under study to be assigned to receive the treatment or not. Under certain causal conditions, including that all confounders of the treatment-outcome relationship are observed, the treatment-specific survival can be identified with a covariate-adjusted survival function. Several e…
Missing attributes are ubiquitous in causal inference, as they are in most applied statistical work. In this paper, we consider various sets of assumptions under which causal inference is possible despite missing attributes and discuss corresponding approaches to average treatment effect estimation, including generalized propensity score methods and multiple imputation. Across an extensive simulation study, we show that no single method systematically out-performs others. We find, however, that doubly robust modifications of standard methods for average treatment effect estimation with missing…
Continuous treatments (e.g., doses) arise often in practice, but many available causal effect estimators are limited by either requiring parametric models for the effect curve, or by not allowing doubly robust covariate adjustment. We develop a novel kernel smoothing approach that requires only mild smoothness assumptions on the effect curve, and still allows for misspecification of either the treatment density or outcome regression. We derive asymptotic properties and give a procedure for data-driven bandwidth selection. The methods are illustrated via simulation and in a study of the effect …
In this paper, we propose a doubly robust method to present the heterogeneity of the average treatment effect with respect to observed covariates of interest. We consider a situation where a large number of covariates are needed for identifying the average treatment effect but the covariates of interest for analyzing heterogeneity are of much lower dimension. Our proposed estimator is doubly robust and avoids the curse of dimensionality. We propose a uniform confidence band that is easy to compute, and we illustrate its usefulness via Monte Carlo experiments and an application to the effects o…
When studying treatment effects in multilevel studies, investigators commonly use (semi-)parametric estimators, which make strong parametric assumptions about the outcome, the treatment, and/or the correlation structure between study units in a cluster. We propose a novel estimator of treatment effects that does not make such assumptions. Specifically, the new estimator is shown to be doubly robust, asymptotically Normal, and often more efficient than existing estimators, all without having to make any parametric modeling assumptions about the outcome, the treatment, and the correlation struct…
In causal inference confounding may be controlled either through regression adjustment in an outcome model, or through propensity score adjustment or inverse probability of treatment weighting, or both. The latter approaches, which are based on modelling of the treatment assignment mechanism and their doubly robust extensions have been difficult to motivate using formal Bayesian arguments, in principle, for likelihood-based inferences, the treatment assignment model can play no part in inferences concerning the expected outcomes if the models are assumed to be correctly specified. On the other…
This paper investigates the problem of making inference about a parametric model for the regression of an outcome variable $Y$ on covariates $(V,L)$ when data are fused from two separate sources, one which contains information only on $(V, Y)$ while the other contains information only on covariates. This data fusion setting may be viewed as an extreme form of missing data in which the probability of observing complete data $(V,L,Y)$ on any given subject is zero. We have developed a large class of semiparametric estimators, which includes doubly robust estimators, of the regression coefficients…
Coarse Structural Nested Mean Models (SNMMs) provide useful tools to estimate treatment effects from longitudinal observational data with time-dependent confounders. Coarse SNMMs lead to a large class of estimators,within which an optimal estimator can be derived under the conditions of well-specified models for the treatment effect, for treatment initiation, and for nuisance regression outcomes (Lok & Griner, 2015). The key assumption lies in a well-specified model for the treatment effect; however, there is no existing guidance to specify the treatment effect model, and model misspecificatio…
Estimation of causal parameters from observational data requires complete confounder adjustment, as well as positivity of the propensity score for each treatment arm. There is often a trade-off between these two assumptions: confounding bias may be reduced through adjustment for a large number of pre-treatment covariates, but positivity is less likely in analyses with irrelevant predictors of treatment such as instrumental variables. Under empirical positivity violations, propensity score weights are highly variable, and doubly robust estimators suffer from high variance and large finite sampl…
Inferring the heterogeneous treatment effect is a fundamental problem in the sciences and commercial applications. In this paper, we focus on estimating Conditional Average Treatment Effect (CATE), that is, the difference in the conditional mean outcome between treatments given covariates. Traditionally, Q-Learning based approaches rely on the estimation of conditional mean outcome given treatment and covariates. However, they are subject to misspecification of the main effect model. Recently, simple and flexible one-step methods to directly learn (D-Learning) the CATE without model specificat…
The Doubly Robust (DR) estimation of ATE can be carried out in 2 steps, where in the first step, the treatment and outcome are modeled, and in the second step the predictions are inserted into the DR estimator. The model misspecification in the first step has led researchers to utilize Machine Learning algorithms instead of parametric algorithms. However, existence of strong confounders and/or Instrumental Variables (IVs) can lead the complex ML algorithms to provide perfect predictions for the treatment model which can violate the positivity assumption and elevate the variance of DR estimator…
We propose a doubly robust approach to characterizing treatment effect heterogeneity in observational studies. We develop a frequentist inferential procedure that utilizes posterior distributions for both the propensity score and outcome regression models to provide valid inference on the conditional average treatment effect even when high-dimensional or nonparametric models are used. We show that our approach leads to conservative inference in finite samples or under model misspecification, and provides a consistent variance estimator when both models are correctly specified. In simulations, …
Many applied decision-making problems have a dynamic component: The policymaker needs not only to choose whom to treat, but also when to start which treatment. For example, a medical doctor may choose between postponing treatment (watchful waiting) and prescribing one of several available treatments during the many visits from a patient. We develop an "advantage doubly robust" estimator for learning such dynamic treatment rules using observational data under the assumption of sequential ignorability. We prove welfare regret bounds that generalize results for doubly robust learning in the singl…
Conditional Distributional Treatment Effects: Doubly Robust Estimation and Testing
Department of Statistics, University of Washington, Seattle, USA（华盛顿大学统计系，美国西雅图）；Departments of Health Care Policy and Statistics, Harvard University, USA（哈佛大学健康政策与统计系，美国）
We revisit the problem of estimating the local average treatment effect (LATE) and the local average treatment effect on the treated (LATT) when control variables are available, either to render the instrumental variable (IV) suitably exogenous or to improve precision. Unlike previous approaches, our doubly robust (DR) estimation procedures use quasi-likelihood methods weighted by the inverse of the IV propensity score - so-called inverse probability weighted regression adjustment (IPWRA) estimators. By properly choosing models for the propensity score and outcome models, fitted values are ens…
In the presence of heterogeneity between the randomized controlled trial (RCT) participants and the target population, evaluating the treatment effect solely based on the RCT often leads to biased quantification of the real-world treatment effect. To address the problem of lack of generalizability for the treatment effect estimated by the RCT sample, we leverage observational studies with large samples that are representative of the target population. This paper concerns evaluating treatment effects on survival outcomes for a target population and considers a broad class of estimands that are …
A Doubly Robust Instrumental Variable Approach for Estimating Average Treatment Effects in Time-to-Event Data with Unmeasured Confounding: Application to Real-World Data on ICU Patients with Septic Shock
We consider the estimation of the average treatment effect in the treated as a function of baseline covariates, where there is a valid (conditional) instrument. We describe two doubly robust (DR) estimators: a locally efficient g-estimator, and a targeted minimum loss-based estimator (TMLE). These two DR estimators can be viewed as generalisations of the two-stage least squares (TSLS) method to semi-parametric models that make weaker assumptions. We exploit recent theoretical results that extend to the g-estimator the use of data-adaptive fits for the nuisance parameters. A simulation study is…
Incorporating External Controls for Estimating the Average Treatment Effect on the Treated with High-Dimensional Data: Retaining Double Robustness and Ensuring Double Safety
DR-VIDAL -- Doubly Robust Variational Information-theoretic Deep Adversarial Learning for Counterfactual Prediction and Treatment Effect Estimation on Real World Data
University of Pittsburgh（匹兹堡大学）；University of Florida（佛罗里达大学）
Unmeasured confounding and selection bias are often of concern in observational studies and may invalidate a causal analysis if not appropriately accounted for. Under outcome-dependent sampling, a latent factor that has causal effects on the treatment, outcome, and sample selection process may cause both unmeasured confounding and selection bias, rendering standard causal parameters unidentifiable without additional assumptions. Under an odds ratio model for the treatment effect, Li et al. 2022 established both proximal identification and estimation of causal effects by leveraging a pair of ne…
Interference occurs when the treatment (or exposure) of one individual affects the outcomes of others. In some settings it may be reasonable to assume individuals can be partitioned into clusters such that there is no interference between individuals in different clusters, i.e., there is partial interference. In observational studies with partial interference, inverse probability weighted (IPW) estimators have been proposed of different possible treatment effects. However, the validity of IPW estimators depends on the propensity score being known or correctly modeled. Alternatively, one can es…
